（来源：康龙化成）
转自：康龙化成
康龙化成举办第五十七期“合成与药物化学前沿”名师线上讲座
2025年7月31日，北京——美国加州斯克利普斯研究所的Keary Engle教授做客康龙化成第五十七期“合成与药物化学前沿”名师线上讲座，报告主题为“程序化烯烃官能化的进展”。报告重点介绍了：1）以烯烃为底物快速且可预测地获取高密度官能化的产品；2）以烯烃为配体增强反应活性或者稳定性。
首先，Keary Engle教授介绍了以烯烃为底物进行多组分联合交叉偶联反应的挑战和研究动力。Keary Engle教授致力于为烯烃 1,2 -双官能化过程构建稳定可控的催化循环，这有助于开发高效的烯烃官能团化反应，拓宽烯烃这类常见化合物的边界和用途，进而为合成化学家提供便利。Keary Engle教授介绍了他们设计的一系列含有引导基团的烯烃底物，引导基团和烯烃上的双键可以与钯或镍络合成具有特定构型的催化循环过渡态，从而催化反应实现具有高反应活性和高区域选择性的烯烃双官能化。
然后，基于含有引导基团的烯烃底物的设计，Keary Engle教授接着介绍了引入手性辅助配体的第二代设计，该体系可以形成低能量的烯烃-镍-芳基过渡态，最终实现烯烃双芳基化的不对称催化。借助计算模拟结果，Keary Engle教授深入浅出地讲解了这个复杂的催化机理。作为此部分的亮点，Keary Engle教授分享了他课题组的研究成果，在实现对映异构体选择性的同时还实现了多种官能团的兼容性。高效的双键不对称催化在药物分子合成中的需求巨大，这种先进的催化方法可以为合成化学家提供更多的思路和手段。
最后，Keary Engle教授介绍了烯烃配体与金属镍络合的预催化剂的稳定性和活性。Engle课题组通过对不同烯烃配体形成的预催化剂的热稳定性和空气稳定性的研究，开发了具有绝对空气稳定性的烯烃配体-镍预催化剂。又进一步研究了不同烯烃配体对反应活性和稳定性的影响，系统性地设计了一系列烯烃配体-镍预催化剂用于适配不同的反应类型，实现了高转化率和选择性。Keary Engle教授还展示了使用烯烃配体-镍预催化剂对双组份烯烃官能团化的催化工作，并研究了烯烃配体在反应过程中的作用，揭示了更多烯烃官能团化的可调控因素和设计思路。
会后，Keary Engle教授在问答环节中与听众进行了热烈的讨论。
Frontiers in Synthetic and Medicinal Chemistry
--The 57th Pharmaron Virtual Lecture
Beijing, China, July 31, 2025 - Pharmaron held its 57th virtual lecture in the Frontiers of Synthetic and Medicinal Chemistry series, delivered by Prof. Keary Englefrom Scripps Research in California.The presentation was titled “Advances in Programmed Alkene Functionalization.” The talk focused on two areas: 1) Using alkene as substrate to afford densely functionalized products in a rapid and predictable way; 2) Using alkene as ligand to enhance reactivity or stability.
Professor Keary Engle started his talk with the introduction of the multi-component conjunctive cross-coupling on alkene substrates and its challenges and research motivations. Professor Keary Engle’s research is focused on establishing catalytic cycle for programmed alkene1,2-difunctionalization and extending the chemical space and usage of alkene as common and accessible substrates. Engle group designed a series of alkene substrates that contained a directing group, in which the directing group and alkene double bond were able to form catalytically-active transitional-state with Ni or Pd metal to afford alkene 1,2-difunctionalization with high reactivity and regioselectivity.
Based on the design of alkene substrates with the directing group, Professor Engle then introduced the 2nd generation design, in which chiral ancillary ligands were added into the system to enable a low-energy transition state of alkene-Ni-aryl complexes and ultimately achieved asymmetric catalysis of alkene diarylation. Exploiting computational results, Professor Engle elucidated the intricate catalytical mechanism. As a highlight of this part, Professor Engle shared an example in which high enantioselectivity and functionalitycompatibility of alkene diarylation were both realized. This advanced catalysis addresses the high demand for efficient asymmetric functionalization of double bond, which is often encountered in drug molecule synthesis.
Professor Keary Engle then discussed stable and reactive alkene ligand-Ni pre-catalysts. Prof. Engle’s group investigated the thermal stability and air stability of pre-catalysts that were formed by different alkene ligands and developed the pre-catalysts with excellent bench-stability. He also demonstrated the impact of alkene ligands to the reactivity and stability. A series of alkene-Ni pre-catalysts were designed systematically to adapt different reactions and had proven to show high conversion and selectivity. Professor Engle also presented catalytical work using alkene-Ni precatalyst and investigated the role of alkene ligand during the reaction that revealed additional tunable factors and design strategies for alkene functionalization.
After the meeting, Professor Keary Engle had a lively discussion with the audience in the Q&A session.
